This application for a Mentored Research Scientist Development Award is designed to provide the candidate, Kanyan Xiao, Instructor of Cell Biology and Dermatology at Emory University, with the opportunity to transit from vascular cell and molecular biology to an independent research area in the field of mouse genetics and vascular tumor biology. This work will be supported by sponsor Dr. Andrew Kowalczyk, an expert in vascular endothelial adhesion, and co-sponsor Dr. Jack Arbiser, a recognized expert in cutaneous vascular pathology. In addition, a strong advisory committee in the area of mouse genetics and vascular endothelial cell biology has been assembled. This project will be carried out in the Department of Cell Biology at Emory University, which has an excellent environment with substantial physical resources and outstanding investigators in the area of both clinical and basic science research, The research project centers on the regulation of VE-cadherin by the armadillo protein p120. VE-cadherin is an important endothelial adhesion molecule that has been implicated in both normal and pathological events including wound healing and vascular tumors. Previous work by the candidate demonstrated that p120 functions as an important regulator of VE-cadherin levels. To investigate the function of p120 in angiogenesis and vascular development, a conditional mouse knock out model system is proposed in which the p120 gene will be specifically ablated in vascular endothelial cells using a Cre-lox strategy. Using this model system, the role of p120 in mouse vascular development and function will be defined. Secondly, the role of p120 in vascular endothelial adhesion and function in vitro will be determined using primary p120 null endothelial cells. Lastly, the effects of p120 downregulation on vascular tumor growth will be evaluated. It is anticipated that the conditional inactivation of p120 in endothelial cells will result in the loss of VE-cadherin expression in endothelial cells in vivo and lead to severe vascular abnormalities. This research will reveal the function of p120 in vivo, and may ultimately reveal new targets for therapies designed to control cutaneous inflammation and angiogenesis. [unreadable] [unreadable] [unreadable]